三七总皂苷对动脉粥样硬化伴急性心肌缺血的综合干预效应与miRNA调控机制研究

Atherosclerosis is the main pathological basis of myocardial ischemia and is one of the fundamental causes of the increase of the incidence of acute cardiovascular events. Angiogenesis is a research focus in the study of myocardial ischemia, however, the abnormal angiogenesis is the potential hazard of atherosclerotic plaque rupture. It has important clinical value and scientific significance to balance the angiogenesis. A large number of clinical and research data show that panax notoginseng and its saponins have good bidirectional regulating effect. Our previous studies also suggested that panax notoginseng saponins had a significant effect on atherosclerosis and myocardial fibrosis. However, its comprehensive intervention effect on atherosclerosis with acute myocardial ischemia has not been reported. So this project aims to replicate atherosclerosis complicated with acute myocardial ischemia double pathological model, focus on angiogenesis, depends on microRNA21 and its target protein maspin/PTEN regulated PI3K/AKT and ERK pathways, with the combination of in vivo and in vitro research strategies and technology to explore the multi-level mechanism of the effects of panax notoginseng saponins prevention and treatment of acute attack of chronic diseases, to provide a reliable experimental basis and scientific theoretical support for its clinical application.

动脉粥样硬化是心肌缺血的主要病理基础，也是急性心血管事件发生率上升的根源之一。血管新生疗法是心肌缺血防治研究的热点领域，然而异常的新生血管又是动脉粥样硬化斑块破裂的潜在危害，兼顾这对矛盾的平衡和统一的治疗方案和药物研究具有重要的临床价值和科学意义。大量临床和研究数据显示，三七及其皂苷制剂具有良好的双向调节作用，课题组前期研究结果也提示三七总皂苷具有显著抗动脉粥样硬化和心肌纤维化的作用，然其对动脉粥样硬化伴急性心肌缺血双重病理情况下的综合干预效应尚缺少报道，我们拟建立动脉粥样硬化伴急性心肌缺血双重病理模型，以血管新生为切入点，以microRNA21及其靶蛋白maspin/PTEN调控的PI3K/AKT和ERK通路为线索，以体内外相结合的研究策略和技术手段进行多层次机制探索，深入研究三七总皂苷防治慢性病变急性发作的效应和生物学内涵，为其临床推广和应用提供可靠的实验依据和科学的理论支撑。

本项目以血管新生在动脉粥样硬化和心肌缺血中的发病机制及不同病理意义为切入点，在动脉粥样硬化伴急性心肌缺血的复杂病理情况下，探讨三七总皂苷对斑块与心肌血管新生可能的双向干预作用及相关机制。通过体内实验，提示三七总皂苷对动脉粥样硬化伴急性心肌缺血具有综合干预效应，三七总皂苷促进缺血心肌血管新生的同时，抑制斑块的血管新生。通过体外实验，结果提示三七总皂苷可以促进内皮细胞的血管新生，且该作用与调控Akt和Erk通路相关。通过本项目的研究，明确三七总皂苷对动脉粥样硬化伴急性心肌缺血具有综合干预效应和可能的机制，为其临床推广和应用提供可靠的实验依据和科学的理论支撑，为中医药多靶点整体调节机体的作用优势提供科学的实验依据。